A Helisch

Johannes Gutenberg-Universität Mainz, Mayence, Rheinland-Pfalz, Germany

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Publications (22)69.56 Total impact

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    ABSTRACT: Ziel/Aim: Following hematopoietic stem cell transplantation, many patients with haematological malignancies suffer from early relapses of their underlying diseases. This is in part due to the insufficiency of the conditioning regimen consisting of chemo- and / or radiotherapy to provide disease control until a sufficient graft-versus-malignancy has been established. By intensifying the local therapy in the bone marrow, radioimmunotherapy (RIT) might help to overcome this lack and thereby improve the prognosis of these patients. We present data from a phase I/II dose escalation study in patients with high-risk disease. Methodik/Methods: 25 patients (3 f, 22 m, mean age 50.6 y, 13 AML, 4 MDS, 4 MM, 2 ALL, 2 CML) underwent dosimetry with 185 MBq indium-111-anti-CD66mAb, whole body scans were conducted with the triple head IRIX camera up to 72 h p.i. Volumes of liver, spleen, kidneys were calculated by CT and used for organ volume correction in OLINDA/EXM 1.1, bone marrow ROIs were drawn manually around the lumbar vertebrae 2-4. Patients were eligible for RIT if dosimetry demonstrated a favourable distribution and residual bone marrow infiltration in biopsy was <20%. For bone marrow, liver and kidneys maximum organ doses allowed by German Radiation Protection Authorities were 35 Gy, 15 Gy and 12 Gy, respectively. Based on 37.5 (n=17) and 45 MBq/kg (n=4) lean body weight RIT was done with a mean of 2.53 ± 0.58 GBq yttrium-90-anti-CD66mAb. Ergebnisse/Results: Calculated doses (Gy/GBq) for bone marrow, spleen, liver and kidneys were 8.72 ± 2.28, 7.73 ± 3.67, 1.50 ± 0.53 and 0.72 ± 0.37, respectively. 4 patients were excluded from radioimmunotherapy due to unfavourable dosimetry (n=3) or labelling failure (n=1). None of the treated patients showed acute side effects of the RIT, no engraftment failure was seen. Schlussfolgerungen/Conclusions: Myeloablative RIT with yttrium-90-anti-CD66mAb was well tolerated, safe and efficient. High bone marrow doses were associated with low burden of relevant nonhaematopoietic organs.
    DGN 2015, Hannover; 04/2015

  • Nuklearmedizin 01/2015; 54(5):197-203. DOI:10.3413/Nukmed-0751-15-06 · 1.49 Impact Factor
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    ABSTRACT: Purpose: Knowledge of the genetic backgrounds of hereditary syndromes, which are increasingly being characterized, enables genetic screening of family members of affected patients. Upon detection of a mutation, genetic counselling and clinical screening including imaging modalities and biochemical analyses are commonly performed. Methods: Unaffected, mutation-positive relatives of index patients with hereditary paraganglioma syndromes were offered PET imaging with [(18)F]fluorodihydroxyphenylalanine and the incidence of pathological findings was retrospectively analysed in relation to mutations of the succinate dehydrogenase enzyme complex. PET only or PET/CT was performed in 21 individuals from eight families with SDHD, one family with SDHC and two families with SDHB mutations. Screening was offered every 2 to 5 years. Results: Of the 21 individuals, 14 showed paraganglioma during screening. In particular, in only 2 of 15 patients with a SDHD mutation were the findings completely unremarkable on PET screening. However, false-negative lesions for abdominal manifestations in two SDHD-positive patients were detected. Conclusion: FDOPA PET is a sensitive imaging modality which should be offered to patients with a detected SDHx (SDHD) mutation, preferably using a hybrid technique.
    European Journal of Nuclear Medicine 02/2013; 40(6). DOI:10.1007/s00259-013-2346-6 · 5.38 Impact Factor
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    ABSTRACT: In somatostatin receptor-targeted therapy, renal toxicity is an expected side effect, and therefore pretherapeutic dosimetry based on a measured kinetics is preferable. In contrast, a convenient one single-time-point scan might also reveal relevant information on expected dose to organs. However, very early time points might not reflect the true retention by the renal cortex and therefore be of limited value to predict dose for the long-lived Lu. Dosimetry with In-octreotide was performed in 24 patients, and the number of disintegrations (ND) were calculated for Lu. Uptake values for each time point were correlated with ND. The fitting algorithm was best with biexponential equations in 18 patients. Mean biologic half-life of the alpha component was 6 hours (+/-12 hours) and for the beta component 82 hours (+/-38 hours). For the early time points, correlation with ND was generally poor. For later time points, correlation increased markedly after 4 hours (4 hours: r = 0.83, 72 hours: r = 0.93) and were also capable of predicting dosimetry to some extent. In conclusion, thorough quantification of the 4 hours single-time-point scans seems to be enough to predict the expected renal dose for radionuclide therapies to some degree.
    Clinical nuclear medicine 08/2012; 37(10):e245-8. DOI:10.1097/RLU.0b013e318248550c · 3.93 Impact Factor
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    ABSTRACT: Differential therapy requires repeated diagnostic assessment for mapping and monitoring of disease activity in Crohn's disease (CD). The purpose of this prospective study was to evaluate the accuracy of (18)F-fluorodexyglucose positron-emission tomography (FDG-PET) for non-invasive assessment of disease activity in CD. Forty-three patients with CD underwent ileocolonoscopy and hydromagnetic resonance imaging (hydro-MRI) as reference standards. In addition, FDG-PET was performed and correlated with clinical data, hydro-MRI, and endoscopy findings. Diagnostic accuracy was determined for all methods. Two-hundred and forty-one bowel segments could be analyzed by all methods. Of 80 endoscopically inflamed segments in CD, FDG-PET detected 72 and hydro-MRI 53 segments. Overall sensitivity was 90 % (FDG-PET) versus 66 % (hydro-MRI), and specificity was 92.6 % versus 99 %. In the proximal ileum, hydro-MRI revealed inflammation in eight out of 49 patients and FDG-PET, also, detected all of these inflamed segments. Seventeen stenoses could be identified in 43 CD patients. With regard to assessment as inflammatory or fibrotic stenosis, there was good concordance between colonoscopy, hydro-MRI, and FDG-PET. In one case only, the nature of the stenosis was assessed differently. In contrast with leukocyte numbers and CDAI, there was significant correlation of FDG-PET activity with C-reactive protein and CDEIS levels (P = 0.019 and P = 0.007, respectively). FDG-PET is able to detect mucosal inflammation in CD with high sensitivity and specificity and to enable proper assessment of inflammatory activity in stenoses. FDG-PET is, thus, a promising non-invasive technique for clinical management of CD.
    Digestive Diseases and Sciences 05/2012; 57(10):2658-68. DOI:10.1007/s10620-012-2190-8 · 2.61 Impact Factor
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    ABSTRACT: Pheochromocytomas (PHEOs) and paragangliomas (PGLs) may be better detected by (18)F-fluorodihydroxyphenylalanine-positron emission tomography (FDOPA-PET) than (123)I-metaiodobenzyl-guanidine (123-I-MIBG) scintigraphy. The objective of the study was to correlate functional imaging results with immunohistochemical, molecular-genetic, and biochemical findings. Thirty consecutive patients with suspected PHEO/PGL presenting at a tertiary referral centre were investigated in a prospective study. Twenty-five patients had confirmed PHEO/PGL. Thirteen of 25 patients had a hereditary PHEO/PGL syndrome (two multiple endocrine neoplasia II, six succinate dehydrogenase complex, subunit D, two succinate dehydrogenase complex, subunit B, one von Hippel Lindau tumor suppressor protein, two Neurofibromatosis-1), and 12 of 25 were classified as sporadic. Five patients had hormonally inactive adrenal incidentalomas. In all patients computed tomography scan and/or magnetic resonance imaging as well as both 123-I-MIBG scintigraphy and FDOPA-PET were performed. Resected tumors were examined by immunohistochemistry for expression of the vesicular monoamine transporter (VMAT)-1 and -2 and other markers. A total of 64 lesions were found with both functional imaging modalities. FDOPA-PET detected 62 lesions, whereas only 34 lesions were detected by 123-I-MIBG scintigraphy. This resulted in an overall sensitivity and specificity for FDOPA-PET of 98 and 100% and for MIBG of 53 and 91%, respectively. Comparable sensitivities were found for adrenal and extraadrenal abdominal lesions (94 vs. 97%), whereas in thoracic/cervical lesions, the sensitivity for 123-I-MIBG scintigraphy (15%) was inferior to that of FDOPA-PET imaging (100%). Immunohistochemistry demonstrated a lack of VMAT-1 expression in all MIBG-negative tumors. Clinical predictors for MIBG negativity were a predominant norepinephrine/normetanephrine secretion, an age less than 45 yr, and a hereditary cause. FDOPA-PET is superior to 123-I-MIBG scintigraphy in patients with extraadrenal, predominantly noradrenaline-secreting, and hereditary types of PHEO/PGL. The lack of VMAT-1 expression predicts negativity for MIBG-scintigraphy.
    The Journal of Clinical Endocrinology and Metabolism 04/2010; 95(6):2800-10. DOI:10.1210/jc.2009-2352 · 6.21 Impact Factor
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    ABSTRACT: Partial volume effects caused by limited spatial resolution of conventional positron emission tomography (PET) scanners result in an underestimation of the activity concentration in small tumours. The aim of the study was to evaluate the feasibility of small animal tumour imaging with the clinical PET scanner ECAT EXACT after partial volume correction based on MRI calculations. The same tumour model was examined additionally with the small animal PET system, microPET focus 120. Before the ECAT EXACT studies recovery coefficients for different sphere volumes were generated with phantom experiments. For the following in-vivo study DS-sarcoma cells were implanted on both hind foot dorsum of male Sprague-Dawley rats. In-vivo tumour volume calculations were done with the high-resolution MRI system, Magnetom Vision Experimental. Dynamic F-fluorodeoxyglucose (FDG) PET was performed with the scanner ECAT EXACT (5 MBq intravenous, two-dimensional mode, n = 16 tumours) or with the microPET focus 120 (20 MBq intravenous, two-dimensional mode, n = 10 tumours). The animals were then killed, the tumours rapidly explanted, weighed and homogenized. The concentration of F-FDG was measured with a gamma counter and decay corrected; the ex-vivo F-FDG concentration was compared with the mean tumour activity concentration of the PET data. Using the ECAT EXACT mean underestimation of actual tumour F-FDG concentration was 35.4%, for partial volume-corrected data this error decreased to 1.7%. In addition, after partial volume correction congruence and linear correlation between the regions of interest-based activity concentration and ex-vivo measurements were excellent (r = 0.98). These results were quite similar to the microPET experiments without partial volume correction: r = 0.99. These data indicate that partial volume correction might allow use of the clinical PET system, ECAT EXACT, for the metabolic assessment of small animal tumours >/=10 mm with sufficient accuracy if no dedicated animal PET is available.
    Nuclear Medicine Communications 12/2009; 31(4):294-300. DOI:10.1097/MNM.0b013e328334fc2a · 1.67 Impact Factor
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    ABSTRACT: The present report examines a new pig model for progressive induction of high-grade stenosis, for the study of chronic myocardial ischemia and the dynamics of collateral vessel growth. Thirty-nine Landrace pigs were instrumented with a novel experimental stent (GVD stent) in the left anterior descending coronary artery. Eight animals underwent transthoracic echocardiography at rest and under low-dose dobutamine. Seven animals were examined by nuclear PET and SPECT analysis. Epi-, mid- and endocardial fibrosis and the numbers of arterial vessels were examined by histology. Functional analysis showed a significant decrease in global left ventricular ejection fraction (24.5 +/- 1.6%) 3 weeks after implantation. There was a trend to increased left ventricular ejection fraction after low-dose dobutamine stress (36.0 +/- 6.6%) and a significant improvement of the impaired regional anterior wall motion. PET and SPECT imaging documented chronic hibernation. Myocardial fibrosis increased significantly in the ischemic area with a gradient from epi- to endocardial. The number of arterial vessels in the ischemic area increased and coronary angiography showed abundant collateral vessels of Rentrop class 1. The presented experimental model mimics the clinical situation of chronic myocardial ischemia secondary to 1-vessel coronary disease.
    Journal of Vascular Research 06/2009; 46(4):290-8. DOI:10.1159/000181545 · 2.90 Impact Factor

  • Experimental and Clinical Endocrinology & Diabetes 01/2007; 115. DOI:10.1055/s-2007-972256 · 1.56 Impact Factor
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    ABSTRACT: [(18)F]FDG-PET was found to be useful for recurrence detection in patients with oral squamous cell carcinoma (OSCC), as a negative PET scan predicted a favorable outcome and survival. Here, we evaluate PET performance in the management of OSCC patients with recurrent/second primary disease after potentially curative second-line therapy. Forty one OSCC patients underwent salvage surgery and 31/41 had received radiation therapy. Thirty five/41 developed recurrent and 6/41 second primary OSCC. Patients had PET evaluation 8.4months (median) after surgery and were followed for at least 6months until disease recurrence or death. For surviving patients, the median follow-up was 33.6months after PET. In OSCC patients who had undergone potentially curative second-line therapy, PET had an overall sensitivity of 85% (92% for recurrence or second primaries, 88% for lymph node failure and 73% for distant metastases). Overall survival was 71% in the PET negative group and 35% in the PET positive group (p<0.01, log-rank test). Moderate glucose metabolism (standardized uptake value4) suggested promising outcome, while SUV>4 indicated a fatal disease course. The data suggest that [(18)F]FDG-PET can facilitate re-staging and clinical management in "high-risk" patients with OSCC.
    Oral Oncology 03/2006; 42(3):297-305. DOI:10.1016/j.oraloncology.2005.08.004 · 3.61 Impact Factor

  • International Journal of Oral and Maxillofacial Surgery 12/2005; 34:15-15. DOI:10.1016/S0901-5027(05)80917-8 · 1.57 Impact Factor
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    ABSTRACT: The new beta2 radioligand (R,R)(S,S) 5-(2-(2-[4-(2-[18F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol ([18F]FE-fenoterol; [18F]FEFE), a fluoroethylated derivative of racemic fenoterol, was evaluated in vivo and ex vivo using a guinea pig model. Dynamic PET studies over 60 min with [(18)F]FEFE were performed in nine Hartley guinea pigs in which a baseline (group 1, n=3), a predose (group 2, n=3; 2 mg/kg fenoterol 5 min prior to injection of [18F]FEFE) or a displacement study (group 3, n=3; 2 mg/kg fenoterol 5 min post injection of [18F]FEFE) was conducted. In all animal groups, the lungs could be visualised and semi-quantified separately by calculating uptake ratios to non-specific binding in the neck area. Premedication with non-radioactive fenoterol and displacement tests showed significant reduction of lung uptake, by 94% and 76%, respectively. These data demonstrate specific binding of the new radioligand to the pulmonary beta2-receptors in accordance with ex vivo measurements. Therefore, [18F]FEFE seems to be suitable for the in vivo visualisation and quantification of the pulmonary beta2-receptor binding in this animal model.
    European journal of nuclear medicine and molecular imaging 12/2005; 32(11):1324-8. DOI:10.1007/s00259-005-1914-9 · 5.38 Impact Factor
  • A Helisch · P Bartenstein ·

    European journal of nuclear medicine and molecular imaging 04/2005; 32(4):513-513. DOI:10.1007/s00259-004-1727-2 · 5.38 Impact Factor
  • I Buchmann · R G Meyer · W Herr · A Helisch · P Bartenstein ·
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    ABSTRACT: The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myeloablative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand.
    Nuklearmedizin 02/2005; 44(3):107-17; quiz N21-2. DOI:10.1267/NUKL05030107 · 1.49 Impact Factor

  • Zeitschrift für Gastroenterologie 01/2005; 43(05). DOI:10.1055/s-2005-920353 · 1.05 Impact Factor

  • Zeitschrift für Gastroenterologie 01/2005; 43(05). DOI:10.1055/s-2005-920132 · 1.05 Impact Factor
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    ABSTRACT: For the internal radiotherapy of neuroendocrine tumours, the somatostatin analogue DOTATOC labelled with 90Y is frequently used [90Y-DOTA-Phe1-Tyr3)-octreotide (SMT487-OctreoTher)]. Radiation exposure to the kidneys is critical in this therapy as it may result in renal failure. The aim of this study was to compare cumulative organ and tumour doses based upon dosimetric data acquired with the chemically identical 86Y-DOTA-Phe1-Tyr3-octreotide (considered as the gold standard) and the commercially available 111In-pentetreotide. The cumulative organ and tumour doses for the therapeutic administration of 13.32 GBq 90Y-DOTA-Phe1-Tyr3-octreotide (three cycles, each of 4.44 GBq) were estimated based on the MIRD concept (MIRDOSE 3.1 and IMEDOSE). Patients with a cumulative kidney dose exceeding 27 Gy had to be excluded from subsequent therapy with 90Y-DOTA-Phe1-Tyr3-octreotide, in accordance with the directives of the German radiation protection authorities. The range of doses (mGy/MBq 90Y-DOTA-Phe1-Tyr3-octreotide) for kidneys, spleen, liver and tumour masses was 0.6-2.8, 1.5-4.2, 0.3-1.3 and 2.1-29.5 (86Y-DOTA-Phe1-Tyr3-octreotide), respectively, versus 1.3-3.0, 1.8-4.4, 0.2-0.8 and 1.4-19.7 (111In-pentetreotide), with wide inter-subject variability. Despite renal protection with amino acid infusions, estimated cumulative kidney doses in two patients exceeded 27 Gy. Compared with 86Y-DOTA-Phe1-Tyr3-octreotide, dosimetry with 111In-pentetreotide overestimated doses to kidneys and spleen, whereas the radiation dose to the tumour-free liver was underestimated. However, both dosimetric approaches detected the two patients with an exceptionally high radiation burden to the kidneys that carried a potential risk of renal failure following radionuclide therapy.
    European journal of nuclear medicine and molecular imaging 11/2004; 31(10):1386-92. DOI:10.1007/s00259-004-1561-6 · 5.38 Impact Factor
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    ABSTRACT: Basaloid squamous cell carcinoma (BSCC) represents a rare but exceptionally aggressive variant of oral cancer. Hence, when tumors have been characterized to belong to this specific high-risk subpopulation, it remains an open issue how to manage the patients in terms of diagnostic surveillance and reconstruction. Therefore we explored whether glucose metabolism as measured by [18F]FDG-PET can accurately assess the disease status in the follow up of oral BSCC. The data of four patients with pathologically proven BSCC were analyzed in this study. These patients had [18F]FDG-PET scans after curative therapy to screen for local recurrence or disease generalization. The [18F]FDG-PET findings were correlated with clinical outcome. [18F]FDG-PET identified a site of recurrent tumor that was invisible to morphological imaging. None of the three patients with a normalized pattern of glucose uptake had secondary tumor progress within the further follow up period. Thus, [18F]FDG-PET proved valuable to identify those patients who will profit from early onset of reconstruction measures even though they originally belonged to a high-risk population.
    Oral Oncology 02/2004; 40(1):56-62. DOI:10.1016/S1368-8375(03)00135-0 · 3.61 Impact Factor
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    ABSTRACT: The (18)F-labeled beta2-adrenergic receptor ligand (R,R)(S,S) 5-(2-(2-[4-(2-[(18)F]fluoroethoxy)phenyl]-1-methylethylamino)-1-hydroxyethyl)-benzene-1,3-diol, a derivative of the original highly selective racemic fenoterol, was synthesized in an overall radiochemical yield of 20% after 65 min with a radiochemical purity higher than 98%. The specific activity was in the range of 50-60 GBq/micromol. In vitro testing of the non-radioactive fluorinated fenoterol derivative with isolated guinea pig trachea was conducted to obtain an IC(50) value of 60 nM. Preliminary ex vivo organ distribution and in vivo experiments with positron emission tomography (PET) on guinea pigs were performed to study the biodistribution as well as the displacement of the radiotracer to prove specific binding to the beta2-receptor.
    Bioorganic & Medicinal Chemistry Letters 09/2003; 13(16):2687-92. DOI:10.1016/S0960-894X(03)00538-9 · 2.42 Impact Factor
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    ABSTRACT: Stenoses are a frequent complication in patients with Crohn's disease and represent a major diagnostic and therapeutic challenge. The proper assessment of the nature of a stenosis as inflammatory or fibrotic is critical for appropriate treatment, since symptomatic fibrotic stenoses require surgical resection. Standard diagnostic procedures to assess the nature of a stenosis include endoscopy, conventional contrast radiography and magnetic resonance tomography. Recent data suggest, that the positron-emission-tomography possesses a high sensitivity and specificity to confirm inflammatory activity in the bowel. The recombinant monoclonal anti-TNF-antibody Infliximab (Remicade) has been approved for the treatment of steroid refractory and steroid dependent Crohn's disease in Germany since 9/2000 and the efficacy of Infliximab is well documented. However, few data exist about the treatment of inflammatory stenoses with Infliximab. We performed a retrospective analysis of our experience with Infliximab in patients with Crohn's disease with special reference to patients with inflammatory stenoses. Among a total of 21 patients treated with Infliximab 11 patients had an inflammatory stenosis. 9 of these patients responded well to Inflimab and became completely asymptomatic for a considerable period of time. Infliximab was tolerated well except for one patient who developed an intrabdominal abscess. The notable clinical response of patients with inflammatory stenoses to Infliximab suggests that treatment with Infliximab might be helpful to postpone or avoid surgical intervention. This finding should be further investigated in a prospective randomized study.
    Zeitschrift für Gastroenterologie 02/2003; 41(1):11-7. · 1.05 Impact Factor